Two component compositions containing zinc amino acid halide complexes and cysteine

ABSTRACT

Provided are compositions, e.g., oral and personal care products, comprising (i) a zinc (amino acid or trialkyl glycine) halide complex, and (ii) cysteine in free or in orally or cosmetically acceptable salt form, together with methods of making and using the same.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation in part of PCT/US2013/46268, filed on18 Jun. 2013; PCT/US2012/70489, filed on 19 Dec. 2012; PCT/US2012/70492,filed on 19 Dec. 2012; PCT/US2012/70498, filed on 19 Dec. 2012;PCT/US2012/70506, filed on 19 Dec. 2012; PCT/US2012/70513, filed on 19Dec. 2012; PCT/US2012/70505, filed on 19 Dec. 2012; PCT/US2012/70501,filed on 19 Dec. 2012; PCT/US2012/70521, filed on 19 Dec. 2012;PCT/US2012/70534, filed on 19 Dec. 2012; and PCT/US2013/50845, filed on17 Jul. 2013, all of which are incorporated herein by reference.

BACKGROUND

Conventional antiperspirants comprising salts of aluminum oraluminum/zirconium are known. These salts function as antiperspirants byforming polymeric complexes which can plug pores, thereby blocking sweatrelease. There is a need for additional antiperspirant active agentsthat provide complexes of a size capable of plugging pores to blocksweat, that provide deodorant/antibacterial efficacy, and that are lessirritating to the skin than the acidic salts in conventionalantiperspirants. There is also a need for alternative antibacterial andskin protective agents for use in liquid hand soaps and body washes.Finally, there is a need for agents in oral care products which canwhiten and strengthen teeth, retard erosion, and inhibit bacteria andplaque.

Certain zinc amino-acid complexes can produce zinc-containingprecipitates upon dilution with water or other aqueous preparations.Some zinc-containing precipitates are composed of zinc oxide, zinchydroxide, zinc halides, etc. The precipitates can be deposited ontoskin as well as hard and soft dental tissues. Potential benefits relatedto deposition on the hard tissues include whitening, sensitivity relief,erosion protection and anticavity. Potential benefits related todeposition on the soft tissue include improvement in the host immuneresponse, enhancement in the tissue's barrier function, etc. Zinc ionscan be released from the depositions, providing antibacterial,bacteriostatic and other plaque and gingivitis benefits as commonlyassociated with zinc ions.

Some zinc ammo-acid complexes, however, do not have the most optimalprecipitation kinetics. In another words, their rate of precipitationupon dilution may be too slow or too fast for typical applications. Forexample, for oral care typical recommended brushing times range from 1minute to 3 minutes, but an average person brushes for a significantlyshorter duration. Typical recommended rinsing times with a mouthrinse isabout a minute, but an average person spends much less time. Some zincamino-acid complex dilutions typically require more than 3 minutes toprecipitate in any substantial quantity, and the amount of precipitationis limited within a typical brushing and rinsing time.

Therefore, there exists a need for optimizing the precipitation times ofzinc complexes. In particular, there is a need for reducing theprecipitation times associated with the zinc amino-acid complexes with aslow precipitation profile.

BRIEF SUMMARY

Provided is a dual component composition to deliver a zinc precipitateto the body which comprises (i) a first component comprising an aqueoussolution of zinc X halide complex (“ZXH”, wherein X refers to an aminoacid or trialkylglycine, “TAG”), and optionally, glycerol and (ii) asecond component comprising acidified cysteine in aqueous solution with,optionally, glycerol; the first and second components being maintainedseparate from each other until dispensed and combined for application tothe body.

The unusual and unexpected properties of this material is that the twocomponents, when mixed, provide a rapid (instant or intentionallydelayed) precipitation that allows the delivery of a zinc-containingcomplex to the body, in particular skin or oral cavity, making it usefulin personal care products, e.g., antiperspirant products and liquid handand body soaps, as well as in oral care products, e.g. mouthwash ordentifrice.

Further areas of applicability of the present invention will becomeapparent from the detailed description provided hereinafter. It shouldbe understood that the detailed description and specific examples, whileindicating the preferred embodiment of the invention, are intended forpurposes of illustration only and are not intended to limit the scope ofthe invention.

DETAILED DESCRIPTION

The following description of the preferred embodiment(s) is merelyexemplary in nature and is in no way intended to limit the invention,its application, or uses.

As used throughout, ranges are used as shorthand for describing each andevery value that is within the range. Any value within the range can beselected as the terminus of the range. In addition, all references citedherein are hereby incorporated by referenced in their entireties. In theevent of a conflict in a definition in the present disclosure and thatof a cited reference, the present disclosure controls.

Unless otherwise specified, all percentages and amounts expressed hereinand elsewhere in the specification should be understood to refer topercentages by weight. The amounts given are based on the active weightof the material.

The zinc (amino acid or TAG) halide complex, i.e., ZXH, can be formed byreacting one or more zinc compounds (e.g.,. zinc oxide, zinc hydroxide,zinc chloride . . . etc., but tetrabasic zinc chloride is specificallyexcluded) and a halide salt of a basic amino acid to obtain a complexhaving the general formula:

Zn-(amino acid or TAG)_(x)-(halide)_(y)

-   -   wherein x is 1-3 and y is 1-3.

In one embodiment, the ZXH is a zinc amino acid halide complex (“ZAH”)such as a zinc-lysine-chloride complex (“ZLC”), e.g., formed from amixture of zinc oxide and lysine hydrochloride, having the formula[Zn(C₆H₁₄N₂O₂)₂Cl]⁺Cl⁻. In this complex, Zn²⁺ is coordinated by twolysine ligands with two N atoms from NH₂ groups and two O atoms fromcarboxylic groups in an equatorial plane. Not wishing to be bound bytheory, it is believed that it displays a distorted square-pyramidalgeometry with the apical position occupied by a Cl⁻ atom. This structuregives rise to a positive cation moiety, to which a Cl⁻ anion is combinedto form an ionic salt.

In another embodiment, the trialkylglycine (TAG) is C₁-C₄ alkylglycineor trimethylglycine.

ZLC may exist in solution of the cationic ([Zn(C₆H₁₄N₂O₂)₂Cl]⁺) and thechloride anion, or may be a solid salt, e.g., a crystal, optionally inmono- or dihydrate form, e.g., as a monohydrate crystal having a powderx-ray diffraction pattern with major peaks having a relative intensityand spacing and spacing substantially as depicted in FIG. 1 ofPCT/US2012/70498.

Other complexes of zinc and amino acid are possible, and the preciseform is dependent in part on the molar ratios of the precursorcompounds, e.g., if there is limited halide, halide-free complexes mayform, e.g. ZnLys₂, having a pyramid geometry, with the equatorial planethat is same as the above compound (Zn is bound to two oxygen and twonitrogen atoms from different lysines), wherein the top of the pyramidis occupied by a Cl atom. Under particular conditions, zinc oxide canalso react with lysine and/or lysine-HCl to form a clear solution ofZn-lysine-chloride complex (ZnLys₃Cl₂), wherein Zn₂ ⁺ is located in anoctahedral center coordinated with two oxygen and two nitrogen atoms inthe equatorial plane coming from two lysine's carboxylic acids and aminegroups respectively. The zinc in this complex is also coordinated to thethird lysine via its nitrogen and carboxylic oxygen, at the apicalposition of the metal geometry. The ZXH complexes, e.g. ZLC, have keyfeatures (e.g., conductivity, hydrolysis reaction and proteinflocculation) which make it competitive with commercial antiperspirantsalts. Like conventional aluminum or aluminum-zirconium antiperspirantsalts, the ZXH forms precipitates that can plug the pores and blocksweat release. As the amount of water increases, the ZXH hydrolyzes todistribute a relatively insoluble zinc-containing precipitate. Theprecipitate typically contains one or more of zinc oxide, zinc cysteine,zinc hydroxide, or other zinc-containing compounds. This precipitate isunique in that it will allow plugging of pores on the skin. Furthermore,this reaction is atypical since, in most cases, dilution will increasethe solubility of an ionic complex. Additionally, zinc is antibacterial,so it provides a precipitate which blocks sweat release from the poreswhile also it providing a deodorant benefit by reducing odor-causingbacteria.

It is important to note that zinc oxide is soluble at low pH, and assweat has a pH of 5-6, the sweat can reduce the levels of precipitationof the zinc oxide compared to precipitation levels at neutral pH.Moreover, the sweat can gradually dissolve the depositions, reducing theduration of action of the formulation. This problem can be amelioratedby co-formulating the product with cysteine. The cysteine and the ZHXtogether form a precipitate. Upon use and dilution with sweat, theprecipitate is more resistant to acid than ZHX alone. The formulationcomprising ZXH together with cysteine thus has enhanced efficacy as anantiperspirant.

We have found that when combining cysteine with ZXH at certain pH's,rapid precipitation is the result. The precipitation is prominent evenin undiluted formulas which results in storage stability problems inoral care or personal care products. Also, rapid precipitation canresult in fewer zinc ions being deposited at desired body sites. We havediscovered that this rapid precipitation problem can be solved byphysically separating the ZHX from the cysteine until use orapplication.

While visible signs of precipitation from some ZLC formulationstypically first appear about 30 minutes or more from dilution, the dualcomponent compositions of the invention form visible precipitates fromless than 1 second to about 20 seconds after mixing the two componentseven in undiluted or low-diluted form. The presence of cysteine resultsin rapid precipitation of zinc complexes. The kinetics or rate ofprecipitation can vary depending on factors such as pH, cysteineconcentration, and amount of dilution (if any). In some embodimentsinstantaneous precipitation of ZXH complexes is observed upon mixing thetwo components. For example, if cysteine is present as approximately0.8-1.3 wt % of a cysteine+ZLC solution, an instantaneous precipitatewill form. As used herein, “rapid precipitation” means forming a zincprecipitate in 3minutes or less, “instant precipitation” or“instantaneous precipitation” means forming a zinc precipitate in Isecond or less, and “delayed precipitation” means forming a zincprecipitate between 1 second and up to 3 minutes.

In preparing the two components of the composition of the invention,typically two stock solutions are prepared, each stock solutioncontaining, respectively ZXH and acidified cysteine. To prepare the twostock solutions, several reagents are necessary. The first component ofthe stock solution can be prepared by utilization of a standardsynthesis procedure for making ZXH. For example, preparing a ZLC stocksolution includes reacting zinc oxide with lysine-HCl over water. Then,excess zinc oxide is filtered off to ultimately make a clear solution.This solution is then the stock of ZLC and can be the main activeingredient in component one. Glycerol can be utilized as a co-solvent incomponent one as well. In the second component, the acidified cysteinestock solution can be prepared by either dissolving cysteine salt indilute aqueous mineral acid, e.g., hydrochloric acid, or cysteine-HClcan be dissolved in water. Glycerol can also be utilized as a co-solventin component two.

A two-component delivery system has been discovered to allow control ofzinc complex precipitation times. The first component comprises ZXH,e.g., ZLC. The pH of the first component is alkaline, for example, about7 to 9, or about 7.25 to about 8.75 or about 7.5 to about 8.5. The pH ofthe second component is acidic, for example, about 3 to about 6 or about4to about 5 or about 4.5 to about 5. The pH of the second component istypically achieved by dissolving the cysteine in an acid, e.g., amineral acid such as a hydrohalide, e.g., hydrochloric acid, and/oracidification can be achieved by dissolving cysteine monohydrohalide,e.g., monohydrochloride, in water, preferably deionized water.

It has been discovered that rapid precipitation of zinc complexes occursat certain pH's, even without dilution. Thus, the pH of the twocomponents when mixed is about 5 to about 8, in another embodiment about5 to about 6.5, in another embodiment about 6 to about 7, and in anotherembodiment about 6 to about 6.5. The pH of each component is tailored toachieve the desired pH upon mixing to result the desired rapid rate ofprecipitation.

The first and second components are aqueous compositions. Typically thefirst component will contain about 1.0 to about 85% water, in anotherembodiment about 20 to about 85% water, in another embodiment about 20to about 25% water, and in yet another embodiment abo 30 to about 33%water. The second component will typically contain about 10% to about95% water, in another embodiment about 20 to about30% water, in anotherembodiment about 90% to about 95%) water. The amount of water in eachcomponent will vary depending upon the final product form in order toachieve the desired concentration when the components are mixed. Forexample, dentifrices typically contain 10 to 25 % total water,mouthwashes typically contain 50 to 90 % total water, personal careproducts such as antiperspirants typically contain 10 to 20%) totalwater. The precipitation time and pH values of the mixtures are affectedby many factors, including water concentration. More water generallyleads to more rapid precipitation and higher pH values of the mixture.

Provided is a dual component composition to deliver zinc to the bodywhich comprises (i) a first component comprising a zinc (amino acid orTAG) halide complex (ZXH) e.g., [Zn(C₆H₁₄N₂O₂)₂Cl]⁺Cl⁻ (ZLC) and (ii) asecond component comprising cysteine in free or in orally orcosmetically acceptable salt form, the first and second components beingmaintained separate from each other until dispensed and combined forapplication to the body. The term “body” includes any site on the bodywhere it is desirable to deposit zinc ions, e.g., skin, in particularpores of sweat glands, and the oral cavity, in particular soft and hard(teeth) tissues. The compositions may be oral care products, e.g.,dentifrice or mouthrinse, or personal care products, such asantiperspirants, liquid hand soap or body wash, and skin lotions, creamsand conditioners.

Upon application of the composition of the invention the firstcomponent, or component one, containing ZXH is mixed with the secondcomponent, or component two, containing acidified cysteine. The weightratio of component one:component two after mixing is typically about1:1, but can vary somewhat depending on the compositions of the specificcomponents and the specific dispensing means used, for example, about5:1 to about 1:5, in another embodiment about 1:2 to about 2:1.

The dual component ZXH/cysteine combination is useful in oral careproducts, for example dentifrice or mouthrinse. A dual componentformulation comprising the ZXH/cysteine combination provides aneffective concentration of zinc ions to the enamel, thereby protectingagainst erosion, reducing bacterial colonization and biofilmdevelopment, and providing enhanced shine to the teeth. Moreover, uponmixing and use, the formulation is diluted and provides a stabilizedprecipitate that plugs the dentinal tubules, thereby reducing thesensitivity of the teeth. While providing efficient delivery of zinc incomparison to formulations with insoluble zinc salts, the formulationscomprising the ZXH/cysteine combination do not exhibit the poor tasteand mouthfeel, poor fluoride delivery, and poor foaming and cleaningassociated with conventional zinc-based oral care products using solublezinc salts.

Further provided are methods of using such compositions, e.g., methodsof reducing sweat comprising applying the composition to skin, methodsof killing bacteria comprising contacting the bacteria with thecomposition, and methods of treating or reducing dentalhypersensitivity, erosion, and plaque, comprising applying thecomposition to the teeth, as well as methods of making suchcompositions. In the methods of the invention the two components of thecomposition of the invention are mixed and applied to the body, e.g.,skin or oral cavity. The mixing is typically performed just before orduring application to the body so that upon application to the body theprecipitate is formed at the desired site, e.g., at pores of sweatglands or at the openings of dentinal tubules. In one embodiment the twocomponents are mixed during application, e.g., brushing with adentifrice where the two components are applied to a toothbrush whichare mixed during brushing. The methods of the invention takes advantageof the property of the precipitate being formed in 3 minutes or lessafter mixing to deliver maximal amount of zinc to the desired bodysites.

In one embodiment, glycerol is added to the first component, secondcomponent or both which results in delay of precipitate formation,typically a delay of about 1 to 20 seconds, in one embodiment about 1 to10 seconds, in another embodiment about 1 to 5 seconds, and in anotherembodiment about 1 to 3 seconds, as compared to a control formulationwithout glycerol. In addition to delaying precipitation, the glycerolcan also function as a humectant.

The mixing can result in precipitation without dilution; however,dilution with water or an aqueous fluid such as saliva or sweatgenerally enhances precipitation. In a particular embodiment, a twocomponent system is provided wherein a first component comprises the ZXHcomplex and the second component comprises cysteine. In thetwo-component system, two containers or chambers are provided containingthe respective components. The cysteine is present in an amounteffective to result in rapid precipitation (instant or delayed) when thetwo components are mixed together. In the delayed precipitationembodiment, just before or during use and application, the twocomponents are mixed whereby the precipitate does not form while mixing,but does form at the desired body location upon application. The twocomponent system is particularly advantageous to maximize the amount ofprecipitation at the desired site during use, e.g., at dentinal tubules,tooth surface, pores of sweat glands, and the like.

The dual component compositions of the present invention, e.g.,dentifrices, body washes or mouthrinses, are packaged in a suitabledispensing container in which the components are maintained physicallyseparated and from which the separated components may be dispensedsynchronously, e.g., as a combined ribbon for application to atoothbrush. Such containers are known in the art. An example of such acontainer is a two compartment dispensing container, such as a pump or atube, having collapsible sidewalks, as disclosed in U.S. Pat. Nos.4,487,757 and 4,687,663; wherein, the tube body is formed from acollapsible plastic web such as polyethylene or polypropylene and isprovided with a partition within the container body defining separatecompartments in which the physically separated components are stored andfrom which they are dispensed through a suitable dispensing outlet. Formouthwashes or mouthrinses, the two components can be delivered by twoseparate chambers of a bottle into a mixing cup. Upon mixing, themixture can be transferred to a human mouth and a rinse can be carriedout. When the components are dispensed, they will mix in the mixing cupforming a slightly delayed precipitate that will react with appropriatekinetics as to ensure all precipitation forms within the mouth.

Provided is, in a first embodiment, a dual component composition(Composition 1) comprising (i) a first component comprising a zinc aminoacid halide complex or a zinc-trialkylglycine halide complex and (ii) asecond component comprising acidified cysteine in free or in orally orcosmetically acceptable salt form, wherein the two components aremaintained separate from each other until dispensed and combined forapplication to the body, e.g.,

-   1.1. Composition 1 wherein the zinc (amino acid or TAG) halide is    formed from precursors, wherein the precursors are a zinc ion    source, an amino acid or TAG source, and a halide source, wherein    the halide source can be part of the zinc ion source, the amino acid    or TAG source, or a halogen acid.-   1.2. Composition 1 or 1.1 wherein the zinc ion source is at least    one of zinc oxide, zinc chloride, zinc carbonate, zinc hydroxide,    zinc nitrate, zinc citrate, and zinc phosphate.-   1.3. Composition 1.1 or 1.3 wherein the amino acid source is at    least one of a basic amino acid, lysine, arginine, and glycine.-   1.4. Any of the foregoing compositions, wherein the trialkyl glycine    is a C₁-C₄ alkyl glycine or trimethyl glycine.-   1.5. Any of the foregoing compositions wherein the pH of the first    component is 3 to 6 or 4 to 5 or 4.5 to 5; and the pH of the second    component is 7 to 9 or 7.25 to 8.75 or 7.5 to 8.5.-   1.6. Any of the foregoing compositions wherein the two components    are mixed and the pH of the resulting mixture is 6 to 8 or 7 to 8.-   1.7. Any of the foregoing compositions wherein the first component    contains 0 to 50% or 20 to 40% glycerol; or the second component    contains 0 to 50% or 20 to 40% glycerol.-   1.8. Any of compositions 1.-1.6 wherein the first component contains    0 to 50% or 20 to 40% glycerol; and the second component contains 0    to 50% or 20 to 40% glycerol.-   1.9. Any of the foregoing Compositions wherein the zinc amino acid    halide is made by combining zinc oxide with an amino acid    hydrohalide.-   1.10. Any of the foregoing Compositions wherein the zinc (amino acid    or TAG) halide has the formula Zn(Amino Acid or TAG)₂Hal₂ or    Zn(Amino Acid or TAG)₃Hal₂, wherein Zn is a divalent zinc ion and    Hal is a halide ion.-   1.11. Any of the foregoing Compositions wherein the zinc amino acid    halide complex is [Zn(C₆H₁₄N₂O₂)₂Cl]⁺Cl⁻ (sometimes referred to    herein as “ZLC”), and wherein when the complex is in crystalline    form, e.g. in hydrate form, e.g. a monohydrate or dihydrate, e.g.,    having a structure wherein the Zn cation is coordinated by two    lysine ligands with two nitrogen atoms from alpha NH₂ groups of the    two lysine ligands and two oxygen atoms from carboxylic groups of    the two lysine ligands in an equatorial plane, having a distorted    square-pyramidal geometry with the apical position occupied by a    chlorine atom, to form a positive cation moiety, with which a    chloride anion is combined to form an ionic salt Composition 1 or    1.1 wherein the zinc-(amino acid or TAG)-halide complex is    [Zn(C₆H₁₄N₂O₂)₂Cl]⁺Cl⁻ (sometimes referred to herein as “ZLC”),    optionally in hydrate form, e.g. a complex formed from a mixture of    zinc oxide and lysine hydrochloride, e.g., in a molar ratio of    ZnO:Lysine-HCl of 1:1 to 3:1, e.g., 2:1.-   1.12. Any of the foregoing Compositions which upon dilution with    water, provides a precipitate comprising zinc oxide in complex with    cysteine, and optionally additionally comprising zinc oxide, zinc    carbonate, and mixtures thereof.-   1.13. Any of the foregoing compositions wherein the total amount of    zinc present in the composition when the two components are mixed is    about 0.2 to about 9%, or about 0.6% to about 1% or about 2% to    about 3% by weight of the total composition.-   1.14. Any of the foregoing composition the about of zinc present in    the first component is about 0.6% to about 2%, or about 0.8% to    about 1.5% or about l% to about 1.2% by weight of the first    component.-   1.15. Any of the foregoing compositions wherein the ratio of zinc to    cysteine is from about 5:1 to about 10:1 by weight of the total    composition-   1.16. Any of the foregoing compositions, wherein the cysteine is a    cysteine hydrohalide, optionally cysteine hydrochloride.-   1.17. Any of the foregoing compositions wherein a zinc precipitate    forms within 30 seconds, or 1 second to 30 seconds, or 1 to 15    seconds or 1 to 3 seconds after mixing the two components.-   1.18. Any of the foregoing compositions further comprising an orally    or cosmetically acceptable carrier in the first component, second    component or both.-   1.19. Any of the foregoing compositions further comprising an orally    or cosmetically acceptable carrier, and which is an oral care    product selected from dentifrice or mouthwash, or a personal care    product, selected from antiperspirants, deodorants, liquid hand    soap, body wash, dermal lotions, dermal creams, and dermal    conditioners.-   1.20. Any of the foregoing compositions wherein the first component    contains about 10% to about 85% water, or about 20 to about 85%    water, or about 20 to about 25% water, or about 30 to about 33%    water; and the second component contains about 10% to about 95%    water or about 20 to about 30% water, or about 40% to about 50%    water.

Provided is a method of making composition 1, et seq. comprising (i)combining a zinc ion source, an amino acid or TAG source, a halidesource (wherein the halide source can be part, of the zinc ion source,the amino acid or TAG source, or a halogen acid), in a fluid (e.g.,aqueous) medium optionally containing glycerol, optionally isolating thecomplex thus formed in solid form and placing the material thus formedinto a first container, (ii) placing cysteine optionally with glycerol,and optionally with a hydrohalide, in a second container physicallyseparate from the first, container. Either or both of the materials inthe separate containers can optionally be combined with a cosmeticallyor orally acceptable carrier.

Provided is a composition (Composition 2) which is an antiperspirant ordeodorant product comprising (i) a first component comprising a zinc(amino acid or TAG) halide complex and (ii) a second componentcomprising acidified cysteine in free or in orally or cosmeticallyacceptable salt form, wherein the two components are maintained separatefrom each other until dispensed and combined for application to thebody, and wherein either or both components additionally comprise acosmetically acceptable carrier, e.g. in accordance with any of thescopes of Composition 1, et seq.

-   2.1. Composition 2 which, upon mixing and use, provides a    precipitate to the skin, comprising zinc oxide in complex with    cysteine, and optionally additionally comprising zinc oxide, zinc    carbonate, and mixtures thereof.-   2.2. Composition 2 or 2.1 wherein zinc (amino acid or TAG) halide    complex is [Zn(C₆H₁₄N₂O₂)₂Cl]⁺Cl⁻ (sometimes referred to herein as    “ZLC”), optionally in hydrate form.-   2.3. Composition 2 or 2.1 wherein the cosmetically acceptable    carrier comprises one or more ingredients selected from    water-soluble alcohols (such as C₂₋₈ alcohols including ethanol);    glycols (including propylene glycol, dipropylene glycol,    tripropylene glycol and mixtures thereof); glycerides (including    mono-, di- and triglycerides); medium to long chain organic acids,    alcohols and esters; surfactants (including emulsifying and    dispersing agents); additional amino acids; structurants (including    thickeners and gelling agents, for example polymers, silicates and    silicon dioxide); emollients; fragrances; and colorants (including    dyes and pigments).-   2.4. Composition 2, 2.1, or 2.2 wherein the composition is in the    form of an aerosol antiperspirant spray.

Also provided are methods of reducing perspiration comprising mixingboth components and applying an antiperspirant effective amount of anyof Composition 2, et seq. to the skin, methods of reducing body odorcomprising mixing both components and applying a deodorant-effectiveamount of any of Composition 2, et seq. to the skin, and methods ofkilling bacteria comprising mixing both components and contacting thebacteria with any of Composition 2, et seq. For example, provided is (i)a method for controlling perspiration comprising mixing both componentsand applying to skin an antiperspirant effective amount of a formulationof any embodiment embraced or specifically described herein, e.g., anyof Composition 2, et seq:, and (ii) a method for controlling odor fromperspiration or bacteria on the skin, comprising mixing both componentsand applying to skin a deodorant effective amount of a formulation ofany embodiment embraced or specifically described herein, e.g., any ofComposition 2, et seq.

Provided is a method of making an antiperspirant or deodorant comprising(i) a first component comprising a zinc (amino acid or TAG) halide and(ii) a second component physically separate from the first componentcomprising cysteine in free or cosmetically acceptable salt form, e.g.,any of Composition 2, et seq. comprising combining a cosmeticallyacceptable carrier, and optionally glycerol, with zinc amino acid halidein the first component, and/or with cysteine in the second component.

Also provided is (i) the use of any of Composition 2, et seq. to kill,bacteria, reduce perspiration, and/or reduce body odor; and (iii) any ofComposition 2, et seq. for use in killing bacteria, reducingperspiration, and/or reducing body odor.

Also provided is the use of cysteine in the manufacture of anantiperspirant or deodorant formulation, e.g., a formulation accordingto any of Composition 2, et seq.

In making Composition 2, et seq. the zinc (amino acid or TAG) halide andcysteine in free or cosmetically acceptable salt form can beincorporated into a suitable, cosmetically acceptable base, for examplea spray, aerosol, stick, or roll-on for application to the underarmwherein the first and second components mix when forming an aerosol orwhen contacted through a nozzle or other dispensing means. Followingapplication, in the presence of charged molecules such as proteins foundon the skin, the salt will flocculate, forming plugs which block sweatrelease. Additional water from sweat can moreover dilute theformulation, causing the complex to decompose, resulting in aprecipitate composed primarily of zinc oxide in complex with cysteine,which can reduce sweat and odor as described above.

As used herein, the term antiperspirant can refer generally to anyproduct that can form a plug in a pore to reduce sweating, includingthose materials classified as antiperspirants by the Food and DrugAdministration under 21 CFR part 350. It is understood thatantiperspirants may also be deodorants, particularly in the case of thedescribed compositions, as zinc has antibacterial properties and thusinhibits odor-causing bacteria on the skin.

Also provided is a composition (Composition 3) which is a personal careproduct selected from liquid hand soap, body wash, dermal lotions,dermal creams, and dermal conditioners comprising (i) a first componentcomprising a zinc (amino acid or TAG) halide complex and (ii) a secondcomponent comprising acidified cysteine in free or in orally orcosmetically acceptable salt form, wherein the two components aremaintained separate from each other until dispensed and combined forapplication to the body, and wherein either or both componentsadditionally comprise a cosmetically acceptable carrier, e.g. inaccordance with any of the scopes of Composition 1, cl sea., e.g.:

-   3.1. Composition 3 which, upon mixture of both components and use,    provides a precipitate to the skin, comprising zinc oxide in complex    with cysteine, and optionally additionally comprising zinc oxide,    zinc carbonate, and mixtures thereof.-   3.2. Composition 3 or 3.1 comprising the zinc (amino acid or TAG)    halide complex in an amount of 1 to 1.0% by weight, of the total    composition.-   2.5. Any of the foregoing compositions wherein the zinc amino acid    halide complex is [Zn(C₆H₁₄N₂O₂)₂Cl]⁺Cl⁻ (sometimes referred to    herein as “ZLC”), optionally in hydrate form.-   3.3. Any of the foregoing compositions, wherein a total amount of    zinc present in the total composition is 0.2 to 8 wt. %, 0.1 to 8    wt. %, 0.1 to 2 wt. % or 0.1 to 1 wt. %.-   3.4. Any of the foregoing compositions, wherein the cysteine is a    cysteine hydrohalide, optionally cysteine hydrochloride.-   3.5. Any of the foregoing compositions wherein the cosmetically    acceptable carrier comprises one or more ingredients selected from    water-soluble alcohols (such, as C₂₋₈ alcohols including ethanol);    glycols (including propylene glycol, dipropylene glycol,    tripropylene glycol and mixtures thereof); glycerides (including    mono-, di- and triglycerides); medium to long chain organic acids,    alcohols and esters; surfactants (including emulsifying and    dispersing agents); additional amino acids; structurants (including    thickeners and gelling agents, for example polymers, silicates and    silicon dioxide); emollients; fragrances; and colorants (including    dyes and pigments).-   3.6. Any of the foregoing compositions, wherein the cosmetically    acceptable carrier comprises one or more nonionic surfactants, for    example non-ionic surfactants selected from amine oxide surfactants    (e.g., fatty acid amides of alkyl amines, for example    lauramidopropyldimethylamine oxide, myristamidopropylamine oxide and    mixtures thereof), alcohol amide surfactants (e.g., fatty acid    amides of alcohol amines, e.g., cocamide MEA    (cocomonoethanolamide)), polyethoxylated surfactants (e.g.    polyethoxylated derivatives of esters of fatty acids and polyols    (for example glycols, glycerols, saccharides or sugar alcohols), for    example polysorbates or PEG-120 methyl glucose dioleate), and    combinations thereof.-   3.7. Any of the foregoing compositions wherein the cosmetically    acceptable carrier comprises an anionic surfactant, e.g. selected    from sodium lauryl sulfate and sodium ether lauryl sulfate.-   3.8. Any of the foregoing compositions wherein the cosmetically    acceptable carrier comprises water, an anionic surfactant, e.g.,    sodium laureth sulfate, a viscosity modifying agent, e.g., acrylates    copolymer, and a zwitterionic surfactant, e.g., cocamidopropyl    betaine.-   3.9. Any of the foregoing compositions wherein the cosmetically    acceptable carrier is substantially free of anionic surfactants.-   3.10. Any of the foregoing compositions wherein the cosmetically    acceptable carrier comprises water, quaternary ammonium agents (e.g.    cetrimonium chloride), humectant (e.g. glycerin), and non-ionic    surfactant (e.g., selected from amine oxide surfactants (e.g.,    lauramidopropyldimethylamine oxide myristamidopropylamine oxide and    mixtures thereof), alcohol amide surfactants (e.g., cocamide MEA    (cocomonoethanolamide)), polyethoxylate surfactants (e.g. PEG-120    methyl glucose dioleate), and combinations thereof).-   3.11. Any of the foregoing compositions, wherein the cosmetically    acceptable carrier comprises an antibacterially effective amount of    a non-zinc antibacterial agent, e.g., an antibacterial agent    selected from triclosan, triclocarban, chloroxylenol, herbal    extracts and essential oils (e.g. rosemary extract, tea extract,    magnolia extract, thymol, menthol, eucalyptol, geraniol, carvacrol,    citral, hinokitol, catechol, methyl salicylate, epigallocatechin    gallate, epigallocatechin, gallic acid), bisguanide antiseptics    (e.g., chlorhexidine, alexidine or octenidine), and quaternary    ammonium compounds (e.g., cetylpyridinium chloride (CPC),    benzalkonium chloride, tetradecylpyridinium chloride (TPC),    N-tetradecyl-4-ethylpyridinium chloride (TDEPC)); and combinations    thereof; for example an antibacterially effective amount of    benzalkonium chloride,-   3.12. Any of the foregoing compositions which has pH of 6-8 when the    two components are mixed.-   3.13. Any of the foregoing compositions comprising ingredients as    follows:

Material Weight % Water 80-90% Quaternary ammonium antibacterial agents,e.g., selected from cetrimonium 0.1-4%   chloride (cetyl trimethylammonium chloride), C₁₂₋₁₈ alkydimethylbenzyl ammonium chloride (BKC),and combinations thereof Humectants, e.g., glycerin 1-3% Non-ionicsurfactant, e.g., selected from amine oxide surfactants (e.g., 1-5%lauramidopropyldimethylamine oxide myristamidopropylamine oxide andmixtures thereof), alcohol amide surfactants (e.g., cocamide MEA(cocomonoethanolamide)), polyethoxylate surfactants (e.g. PEG-120 methylglucose dioleate), and combinations thereof Buffering agents and agentsto adjust pH 1-3% Preservatives and/or chelators 0.1-2%   Fragrance andcoloring agents 0.1-2%   ZLC 1-5%, e.g., 3-4% Cysteine 0.1-1%, e.g. 0.5%wherein the formulation is in a container that has a divided chamber;one chamber containing the above base with cysteine and the othercontaining the above base with ZLC.

Also provided are methods of killing bacteria comprising mixing bothcomponents and contacting the bacteria with an antibacterially effectiveamount of the mixture, e.g., with any of Composition 3, et seq,, forexample, methods of treating or reducing the incidence of topical skininfections, for example infections by Staphylococcus aureus and/orStreptococcus pyogenes, as well as to treat or reduce the incidence ofacne, comprising washing the skin with an antibacterially effectiveamount of a ZLC and cysteine, e.g., with any of Composition 3, et seq.,and water.

Also provided is a method of making a personal care comprising (i) afirst component comprising a zinc (amino acid or TAG) halide and (ii) asecond component physically separate from the first component comprisingcysteine in free or cosmetically acceptable salt form, e.g., any ofComposition 3, et seq. comprising combining a cosmetically acceptablecarrier, and optionally glycerol, with zinc amino acid halide in thefirst component, and/or with cysteine in the second component.

Also provided is (i) the use of a dual component composition containingZXH complex and cysteine, e.g., any of Compositions 1, et seq., to killbacteria, to protect the skin, e.g., from bacteria or to provide avisual signal when washing; (ii) the use of a ZLC and cysteine in themanufacture of a composition, any of Compositions 1, et seq., to killbacteria, to protect the skin, or to provide a visual signal whenwashing; and (iii) ZLC and cysteine, e.g., any of Compositions 1, etseq., for use to kill bacteria, to protect the skin, or to provide avisual signal when washing.

For example, in one embodiment, either the first component comprisingthe zinc (amino acid or TAG) complex or the second component comprisingthe cysteine, or both are mixed with conventional commercial liquid handsoap formulation ingredients comprising surfactants and optionallybenzalkonium chloride. Upon mixing both components and dilution a whiteprecipitate is instantaneously formed. Thus, the composition of theinvention can provide a visual/sensory trigger for the washing process.The precipitate, composed of ZnO stabilized by cysteine, is deposited onskin and thus enhances the antimicrobial effect of the LHS.

Also provided is a composition (Composition 4) which is an oral careproduct, e.g., a dentifrice or mouthrinse, comprising (i) a firstcomponent comprising a zinc (amino acid or TAG) halide complex and (ii)a second component comprising acidified cysteine in free or in orally orcosmetically acceptable salt form, wherein the two components aremaintained separate from each other until dispensed and combined forapplication to the oral cavity, and wherein either or both componentsadditionally comprise an orally acceptable carrier, e.g. in accordancewith any of the scopes of Composition 1, et seq., e.g.:

-   4.1. Composition 4 in the form of a dentifrice which upon mixing and    application to the teeth provides a precipitate to the teeth,    comprising zinc oxide in complex with cysteine, and optionally    additionally comprising zinc oxide, zinc carbonate, and mixtures    thereof.-   4.2. Composition 4 or 4.1 in the form of a dentifrice wherein the    zinc (amino acid or TAG) halide complex is present in an effective    amount, e.g., in an amount of 0.5-4% by weight of zinc, e.g., 1-3%    by weight of zinc of the total composition, and wherein the orally    acceptable carrier is a dentifrice base.-   4.3. Any of the foregoing compositions wherein the zinc amino acid    halide complex is [Zn(C₆H₁₄N₂O₂)₂Cl]⁺Cl⁻ (sometimes referred to    herein as “ZLC”), optionally in hydrate form.-   4.4. Any of the foregoing compositions 4-4.3 in the form of a    dentifrice, wherein the orally acceptable carrier is a dentifrice    base comprising an abrasive, e.g., an effective amount of a silica    abrasive, e.g., 10-30%, e.g., 20%).-   4.5. Any of the foregoing compositions wherein the zinc amino acid    halide complex is present in an effective amount, e.g., in an amount    of 0.1-3% by weight of zinc, e.g., 0.2-1% by weight of zinc of the    total composition.-   4.6. Any of the foregoing compositions, wherein the cysteine is a    cysteine hydrohalide, optionally cysteine hydrochloride.-   4.7. Any of the foregoing compositions further comprising an    effective amount of a fluoride ion source, e.g., providing 500 to    3000 ppm fluoride based on the total composition.-   4.8. Any of the foregoing compositions further comprising an    effective amount of fluoride, e.g., wherein the fluoride is a salt    selected from stannous fluoride, sodium fluoride, potassium    fluoride, sodium monofluorophosphate, sodium fluorosilicate,    ammonium fluorosilicate, amine fluoride (e.g.,    N′-octadecyltrimethylendiamine-N,N,N′-tris(2-ethanol)-dihydrofluoride),    ammonium fluoride, titanium fluoride, hexafluorosulfate, and    combinations thereof.-   4.9. Any of the preceding compositions comprising an effective    amount of one or more alkali phosphate salts, e.g., sodium,    potassium or calcium salts, e.g., selected from alkali dibasic    phosphate and alkali pyrophosphate salts, e.g., alkali phosphate    salts selected from sodium phosphate dibasic, potassium phosphate    dibasic, dicalcium phosphate dihydrate, calcium pyrophosphate,    tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium    tripolyphosphate, and mixtures of any of two or more of these, e.g.,    in an amount of 1-20%, e.g., 2-8%), e.g., ca. 5%, by weight of the    composition.-   4.10. Any of the foregoing compositions comprising buffering agents,    e.g., sodium phosphate buffer (e.g., sodium phosphate monobasic and    disodium phosphate).-   4.11. Any of the foregoing compositions comprising a humectant,    e.g., selected from sorbitol, propylene glycol, polyethylene glycol,    xylitol, and mixtures thereof. Any of the preceding compositions    comprising one or more surfactants, e.g., selected from anionic,    cationic, zwitterionic, and nonionic surfactants, and mixtures    thereof e.g., comprising an anionic surfactant, e.g., a surfactant    selected from sodium lauryl sulfate, sodium ether lauryl sulfate,    and mixtures thereof, e.g. in an amount of from 0.3% to 4.5% by    weight, e.g. 1-2% sodium lauryl sulfate (SLS); and/or a zwitterionic    surfactant, for example a betaine surfactant, for example    cocamidopropylbetaine, e.g. in an amount of from 0.1% to 4.5% by    weight of the total composition, e.g. 0.5-2% cocamidopropylbetaine.-   4.12. Any of the preceding compositions further comprising a    viscosity modifying amount of one or more of polysaccharide gums,    for example xanthan gum or carrageenan, silica thickener, and    combinations thereof.-   4.13. Any of the preceding compositions comprising gum strips or    fragments.-   4.14. Any of the preceding compositions further comprising    flavoring, fragrance and/or coloring.-   4.15. Any of the foregoing compositions comprising an effective    amount of one or more antibacterial agents, for example comprising    an antibacterial agent selected from halogenated diphenyl ether    (e.g. triclosan), herbal extracts and essential oils (e.g., rosemary    extract, tea extract, magnolia extract, thymol, menthol, eucalyptol,    geraniol, carvacrol, citral, hinokitol, catechol, methyl salicylate,    epigallocatechin gallate, epigallocatechin, gallic acid, miswak    extract, sea-buckthorn extract), bisguanide antiseptics (e.g.,    chlorhexidine, alexidine or octenidine), quaternary ammonium    compounds (e.g., cetylpyridmium chloride (CPC), benzalkonium    chloride, tetradecylpyridinium chloride (TPC),    N-tetradecyl-4-ethylpyridium chloride (TDEPC)), phenolic    antiseptics, hexetidine, octenidine, sanguinarine, povidone iodine,    delmopinol, salifluor, metal ions (e.g., zinc salts, for example,    zinc citrate, stannous salts, copper salts, iron salts),    sanguinarine, propolis and oxygenating agents (e.g., hydrogen    peroxide, buffered sodium peroxyborate or peroxycarbonate), phthalic    acid and its salts, monoperthalic acid and its salts and esters,    ascorbyl stearate, oleoyl sarcosine, alkyl sulfate, dioctyl    sulfosuccinate, salicylanilide, domiphen bromide, delmopinol,    octapinol and other piperidino derivatives, nicin preparations,    chlorite salts; and mixtures of any of the foregoing; e.g.,    comprising triclosan or cetylpyridmium chloride.-   4.16. Any of the foregoing compositions comprising an    antibacterially effective amount of triclosan, e.g. 0.1-0.5%, e.g.    0.3% by weight of the total composition.-   4.17. Any of the preceding compositions further comprising a    whitening agent, e.g., a selected from the group consisting of    peroxides, metal chlorites, perborates, percarbonates, peroxyacids,    hypochlorites, and combinations thereof.-   4.18. Any of the preceding compositions further comprising hydrogen    peroxide or a hydrogen peroxide source, e.g., urea peroxide or a    peroxide salt or complex (e.g., such as peroxyphosphate,    peroxycarbonate, perborate, peroxysilicate, or persulphate salts;    for example calcium peroxyphosphate, sodium perborate, sodium    carbonate peroxide, sodium peroxyphosphate, and potassium    persulfate);-   4.19. Any of the preceding compositions further comprising an agent    that interferes with or prevents bacterial attachment, e.g., solbrol    or chitosan.-   4.20. Any of the preceding compositions further comprising a source    of calcium and phosphate selected from (i) calcium-glass complexes,    e.g., calcium sodium phosphosilicates, and (ii) calcium-protein    complexes, e.g., casein phosphopeptide-amorphous calcium phosphate-   4.21. Any of the preceding compositions further comprising a soluble    calcium salt, e.g., selected from calcium sulfate, calcium chloride,    calcium nitrate, calcium acetate, calcium lactate, and combinations    thereof.-   4.22. Any of the preceding compositions further comprising a    physiologically or orally acceptable potassium salt, e.g., potassium    nitrate or potassium chloride, in an amount effective to reduce    dentinal sensitivity.-   4.23. Any of the foregoing compositions further comprising an    anionic polymer, e.g., a synthetic anionic polymeric    polycarboxylate, e.g., wherein the anionic polymer is selected from    1:4 to 4:1 copolymers of maleic anhydride or acid with another    polymerizable ethylenically unsaturated monomer; e.g., wherein the    anionic polymer is a methyl vinyl ether/maleic anhydride (PVM/MA)    copolymer having an average molecular weight (M.W.) of 30,000 to    1,000,000, e.g. 300,000 to 800,000, e.g., wherein the anionic    polymer is 1-5%, e.g., 2%, of the weight of the total composition.-   4.24. Any of the preceding compositions further comprising a breath    freshener, fragrance or flavoring.-   4.25. Any of the foregoing compositions, wherein the pH of the total    composition is approximately neutral, e.g., from pH 5 to pH 8 e.g.,    pH 7.-   4.26. Any of the foregoing compositions in the form of an oral gel,    wherein the amino acid is lysine and the zinc and lysine form a zinc    amino acid halide complex having the chemical structure    [Zn(C₆H₁₄N₂O₂)₂Cl]⁺ Cl⁻, in an amount to provide 0.1-8%, e.g., 0.5%    zinc by weight, and further comprising humectant, e.g., sorbitol,    propylene glycol and mixtures thereof, e.g., in an amount of 45-65%,    e.g., 50-60%, thickeners, e.g., cellulose derivatives, e.g.,    selected from carboxymethyl cellulose (CMC), trimethyl cellulose    (TMC) and mixtures thereof, e.g., in an amount of 0.1-2%, sweetener    and/or flavorings, and water, e.g., an oral gel comprising

Ingredients % Sorbitol 40-60%, e.g., 50-55% ZLC to provide 0.1-2% Zn,e.g 0.5% Zn Cysteine 0.02-0.5%, e.g., 0.1% Carboxymethyl cellulose (CMC)and 0.5-1%, e.g., 0.7% Trimethyl cellulose (TMC) Flavoring and/orsweetener 0.01-1% Propylene Glycol 1-5%, e.g., 3.00%wherein the formulation is in a tube that has a dual chamber system thatseparates one side from the other; or, the system has a high enoughdensity difference that allows for almost complete separation of the twostocks or components.

-   4.27. Any of the forgoing compositions for use to reduce and inhibit    acid erosion of the enamel, clean the teeth, reduce    bacterially-generated biofilm and plaque, reduce gingivitis, inhibit    tooth decay and formation of cavities, and reduce dentinal    hypersensitivity.

The dentifrice of the invention can be placed in a dual chamber tube,each chamber containing one of the respective components. Each componentcan contain a dentifrice base, e.g., a gel base, as well as eithercysteine or ZLC. When the tube is squeezed both reagents will come outat the same time and mixing will take place in-vitro while brushing withthe aid of the dentifrice base.

Also provided are methods to reduce and inhibit acid erosion of theenamel, clean the teeth, reduce bacterially-generated biofilm andplaque, reduce gingivitis, inhibit tooth decay and formation ofcavities, and reduce dentinal hypersensitivity, comprising mixing bothcomponents and applying an effective amount of a composition, e.g., anyof Composition 4, et seq. to the teeth, and optionally then rinsing withwater or aqueous solution sufficient to enhance precipitation of zincoxide in complex with cysteine from the composition.

Also provided is a method of making a an oral care product, e.g., adentifrice or mouthrinse, comprising (i) a first component comprising azinc (amino acid or TAG) halide and (ii) a second component physicallyseparate from the first component comprising cysteine in free orcosmetically acceptable salt form, e.g., any of Composition 4, et seq.comprising combining an orally acceptable carrier, and optionallyglycerol, with zinc amino acid halide in the first component, and/orwith cysteine in the second component.

For example, in various embodiments, provided are methods to (i) reducehypersensitivity of the teeth, (ii) to reduce plaque accumulation, (iii)reduce or inhibit demineralization and promote remineralization of theteeth, (iv) inhibit microbial biofilm formation in the oral cavity, (v)reduce or inhibit gingivitis, (vi) promote healing of sores or cuts inthe mouth, (vii) reduce levels of acid producing bacteria, (viii) toincrease relative levels of non-cariogenic and/or non-plaque formingbacteria, (ix) reduce or inhibit formation of dental caries, (x),reduce, repair or inhibit pre-carious lesions of the enamel, e.g., asdetected by quantitative light-induced fluorescence (QLF) or electricalcaries measurement (ECM), (xi) treat, relieve or reduce dry mouth, (xii)clean the teeth and oral cavity, (xiii) reduce erosion, (xiv) whitenteeth; (xv) reduce tartar build-up, and/or (xvi) promote systemichealth, including cardiovascular health, e.g., by reducing potential forsystemic infection via the oral tissues, comprising mixing bothcomponents and applying any of Compositions 4, et seq. as describedabove to the oral cavity of a person in. need thereof, e.g., one or moretimes per day. Also provided are Compositions 4, et seq. for use in anyof these methods.

Also provided is the use of (i) a ZXH complex, and (ii) cysteine in freeor orally acceptable salt form in the manufacture of an oral carecomposition, e.g., in accordance with any of Compositions 4, et seq.

Also provided is the use of (i) a ZXH complex, and (ii) cysteine in freeor orally acceptable salt form, to reduce and inhibit acid erosion ofthe enamel, clean the teeth, reduce bacterially-generated biofilm andplaque, reduce gingivitis, inhibit tooth decay and formation ofcavities, and/or reduce dentinal hypersensitivity.

In one embodiment, the ZXH complex is prepared at room temperature bymixing the precursors in an aqueous solution. The in situ formationprovides ease of formulation. The precursors can be used instead offirst having to form the salt. In another embodiment, the waterpermitting formation of the salt from the precursor comes from water(e.g., rinsing water, saliva or sweat, depending on the application)that comes into contact with the composition in the course of use.

In some embodiments, the total amount of zinc in the composition is 0.05to 8% by weight of the total composition. In other embodiments, thetotal amount of zinc is at least 0.1, at least 0.2, at least 0.3, atleast 0.4, at least 0.5, or at least 1 up to 8% by weight of the totalcomposition. In other embodiments, the total amount of zinc in thecomposition is less than 5, less than 4, less than 3, less than 2, orless than 1 to 0.05% by weight of the total composition. For example,the zinc content may be 2-3%.

In certain embodiments, the ZHX complex is anhydrous for dentifricecompositions that contain less than 10% water by weight. By anhydrous,there is less than 5% by weight water, optionally less than 4, less than3, less than 2, less than 1, less than 0.5, less than 0.1 down to 0% byweight water. When provided in an anhydrous form, precursors of zincamino acid halide complex, e.g., zinc oxide and lysine hydrochloride,will not significantly react. When contacted with a sufficient amount ofwater, the precursors will then react to form the desired salt, e.g.,ZLC, which upon further dilution with use forms the desired precipitateon the skin or teeth.

X Moiety:

The X moiety in the ZXH complex can be an amino acid or trialkylglycine,preferably glycine betaine. The amino acid in the zinc amino acid halidecomplex can be a basic amino acid. By “basic amino acid” is meant thenaturally occurring basic amino acids, such as arginine, lysine, andhistidine, as well as any basic amino acid having a carboxyl group andan amino group in the molecule, which is water-soluble and provides anaqueous solution with a pH of 7 or greater. Accordingly, basic aminoacids include, but are not limited to, arginine, lysine, citrulline,ornithine, creatine, histidine, diaminobutanoic acid, diaminoproprionicacid, salts thereof or combinations thereof. In a particular embodiment,the basic amino acid is lysine. The basic amino acids for use in makingzinc amino acid halide complex are generally provided in the form of thehalide acid addition salt, e.g., a hydrochloride.

Trialkyl glycine possesses a quaternary ammonium structure. The alkylgroups are, independently, C₁₋₄ straight chain or branched alkyl groups.A preferred trialkyl glycine is N,N,N-trimethylglycine (also known asTMG, glycine betaine, or trimethyglycine). At neural pH, the compoundexists as a zwitterion, forming an inner salt between the quaternaryammonium and the carboxy portions of the molecule. In the presence ofstrong acids, it will form acid addition salts, e.g., hydrochloride. Thecompound is originally isolated from sugar beets, and is used as adietary supplement in animal feed and as a laboratory reagentstabilizer, e.g., in polymerase chain reactions.

Glycerol

Glycerol or glycerin is an optional ingredient in the first and/orsecond component of the composition. It has found that the presence ofglycerol can delay the precipitation of the ZXH complex when the twocomponents are mixed. Glycerol can also act as a humectant.

Cysteine

The compositions also comprise cysteine in free or orally orcosmetically acceptable salt form. By “orally or cosmetically acceptablesalt form” is meant a salt form which is safe for administration to theoral cavity or skin respectively in the concentrations provided, andwhich does not interfere with the biological activity of the zinc. In aparticular embodiment, the cysteine is administered in free form.Wherever weights are given for amounts of amino acids in formulationsherein, the weights are generally provided in terms of the weight of thefree acid unless otherwise noted. In certain embodiments, the cysteineis a cysteine hydrohalide, such as cysteine hydrochloride.

In compositions comprising an orally or cosmetically acceptable carrier,the carrier represents all other materials in the composition other thanzinc amino acid halide complex (including precursors) and the cysteine.The amount of carrier is thus the amount to reach 100% by adding to theweight of zinc amino acid halide complex (including precursors) and theprotein. By “orally acceptable carrier” is meant a carrier which issuitable for use in an oral care product, consisting of ingredientswhich are generally recognized as safe for use in amounts andconcentrations as provided in a dentifrice or mouthrinse, for example.By “cosmetically acceptable carrier” is meant a carrier which issuitable for use in a product for topical use on the skin, consisting ofingredients which are generally recognized as safe for use in amountsand concentrations as provided in a liquid hand soap or body wash, or inan antiperspirant product, for example. Excipients for use in thecompositions thus may include for example excipients which are“Generally Recognized as Safe” (GRAS) by the United States Food and DrugAdministration.

Personal Care Formulations:

The term “cosmetically acceptable carrier” thus refers to anyformulation or carrier medium that provides the appropriate delivery ofan effective amount of the complex as defined herein, does not interferewith the effectiveness of the biological activity of the zinc, and issuitable and nontoxic for topical administration to the skin.Representative carriers include water, oils, both vegetable and mineral,soap bases, cream bases, lotion bases, ointment bases and the like,particularly aqueous detergent carriers, for example liquid hand soapsor body washes. In one embodiment, the aqueous soap bases are free of orcontain less than one percent of anionic surfactants. In anotherembodiment, the cosmetically acceptable carrier contains topicallyacceptable quaternary ammonium compounds. They may additionally includebuffers, preservatives, antioxidants, fragrances, emulsifiers, dyes andexcipients known or used in the field of drug formulation and that donot unduly interfere with the effectiveness of the biological activityof the active agent, and that is sufficiently non-toxic to the host orpatient. Additives for topical formulations are well-known in the art,and may be added to the topical composition, as long as they arepharmaceutically acceptable and not deleterious to the epithelial cellsor their function. Further, they should not cause deterioration in thestability of the composition. For example, inert fillers,anti-irritants, tackifiers, excipients, fragrances, opacifiers,antioxidants, gelling agents, stabilizers, surfactant, emollients,coloring agents, preservatives, buffering agents, and other conventionalcomponents of topical formulations as are known in the art.

In some cases, the personal care compositions comprise oils ormoisturizers, which may not be water soluble and may be delivered in anemulsion system, wherein the zinc-lysine complex would be in the waterphase of the emulsion. Surfactants for the emulsion formulations maycomprise a combination of nonionic surfactants, for example, one or moresurfactants selected from the group consisting of: (i) lipophilicsurfactants, e.g., having an HLB value of 8 or lower, for examplesorbitan-fatty acid esters, such as sorbitan oleates, for example,sorbitan sesquioleate; and (ii) hydrophilic surfactants, e.g., having anHLB of greater than 8, particularly a. di- or tri-alkanol amines, suchas methanol amine; b. polyethoxylated surfactants, for examplepolyethoxylated alcohols (esp. polyethoxylated polyols), polyethoxylatedvegetable oils, and polyethoxylated silicones, e.g., polysorbate 80,dimethicone polyethylene oxide, and dimethylmethyl (polyethylene oxide)siloxane. For a water-in-oil emulsion, the overall HLB of the surfactantmixture is preferably 2-8, i.e., there is typically a higher proportionof lipophilic surfactant; whereas for an oil-in-water emulsion, theoverall HLB of the surfactant mixture is preferably 8-16.

The personal care compositions may also comprise suitable antioxidants,substances known to inhibit oxidation. Antioxidants suitable for use inthe compositions include, but are not limited to, butylatedhydroxytoluene, ascorbic acid, sodium ascorbate, calcium ascorbate,ascorbic palmitate, butylated hydroxyanisole,2,4,5-trihydroxybutyrophenone, 4-hydroxymethyl-2,6-di-tert-butylphenol,erythorbic acid, gum guaiac, propyl gallate, thiodipropionic acid,dilauryl thiodipropionate, tert-butylhydroquinone and tocopherols suchas vitamin E, and the like, including pharmaceutically acceptable saltsand esters of these compounds. Preferably, the antioxidant is butylatedhydroxytoluene, butylated hydroxyanisole, propyl gallate, ascorbic acid,pharmaceutically acceptable salts or esters thereof or mixtures thereof.Most preferably, the antioxidant is butylated hydroxytoluene. Thesematerials are available from Ruger Chemical Co, (Irvington, N.J.). Whenthe topical formulations contain at least one antioxidant, the totalamount of antioxidant present is from 0.001 to 0.5 wt %, preferably 0.05to 0.5 wt %, more preferably 0.1%.

The personal care compositions may also comprise suitable preservatives.Preservatives are compounds added to a formulation to act as anantimicrobial agent. Among preservatives known in the art as beingeffective and acceptable in parenteral formulations are benzalkoniumchloride, benzethonium, chlorohexidine, phenol, m-cresol, benzylalcohol, methylparaben, propylparaben, chlorobutanol, o-cresol,p-cresol, chlorocresol, phenylmercuric nitrate, thimerosal, benzoicacid, and various mixtures thereof. See, e.g., Wallhausser, K.-H.,Develop. Biol. Standard, 24:9-28 (1974) (S. Krager, Basel). Preferably,the preservative is selected from methylparaben, propylparaben andmixtures thereof. These materials are available from Inolex Chemical Co(Philadelphia, Pa.) or Spectrum Chemicals. When the topical formulationscontain at least one preservative, the total amount of preservativepresent is from 0.01 to 0.5 wt %, preferably from 0.1 to 0.5%, morepreferably from 0.03 to 0.15. Preferably the preservative is a mixtureof methylparaben and proplybarben in a 5/1 ratio. When alcohol is usedas a preservative, the amount is usually 15 to 20%.

The personal care compositions may also comprise suitable chelatingagents to form complexes with metal cations that do not cross a lipidbilayer. Examples of suitable chelating agents include ethylene diaminetetraacetic acid (EDTA), ethylene glycol-bis(beta-aminoethylether)-N,N,N′, N′ -tetraacetic acid (EGTA) and8-Amino-2-[(2-amino-5-methylphenoxy)methyl]-6-methoxyquinoline-N₅N,N′,N′-tetraaceticacid, tetrapotassium salt (QUIN-2). Preferably the chelating agents areEDTA and citric acid. These materials are available from SpectrumChemicals. When the topical formulations contain at least one chelatingagent, the total amount of chelating agent present is from 0.005% to2.0%) by weight, preferably from 0.05% to 0.5 wt %, more preferably 0.1% by weight. Care must be taken that the chelators do not interfere withthe zinc complex, for example by binding zinc, but in the formulationstested, low levels of EDTA, for example, have not presented problems.

The personal care compositions may also comprise suitable pH adjustingagents and/or buffers to adjust and maintain the pH of the formulationto a suitable range, e.g., pH 6-8 or approximately neutral pH.

The personal care compositions may also comprise suitable viscosityincreasing agents. These components are diffusible compounds capable ofincreasing the viscosity of a polymer-containing solution through theinteraction of the agent with the polymer. CARBOPOL ULTREZ 10 may beused as a viscosity-increasing agent. These materials are available fromNoveon Chemicals, Cleveland, Ohio, When the topical formulations containat least one viscosity increasing agent, the total amount of viscosityincreasing agent present is from 0.25% to 5.0% by weight, preferablyfrom 0,25% to 1.0 wt %, and more preferably from 0.4% to 0.6% by weight.

Liquid forms, such as lotions suitable for topical administration orsuitable for cosmetic application, may include a suitable aqueous ornonaqueous vehicle with buffers, suspending and dispensing agents,thickeners, penetration enhancers, and the like. Solid forms such ascreams or pastes or the like may include, for example, any of thefollowing ingredients, water, oil, alcohol or grease as a substrate withsurfactant, polymers such as polyethylene glycol, thickeners, solids andthe like. Liquid or solid formulations may include enhanced deliverytechnologies such as liposomes, microsomes, microsponges and the like.

Topical treatment regimens can comprise applying the compositiondirectly to the skin at the application site, from one to several timesdaily, and washing with water to trigger precipitation of the zinc oxideon the skin.

Formulations can be used to treat, ameliorate or prevent conditions orsymptoms associated with bacterial infections, acne, inflammation andthe like.

Oral Care Formulations

The oral care compositions, e.g., Composition 4, et seq. may comprisevarious agents which are active to protect and enhance the strength andintegrity of the enamel and tooth structure and/or to reduce bacteriaand associated tooth decay and/or gum disease, including or in additionto the zinc-ammo acid-halide complexes. Effective concentration of theactive ingredients used herein will depend on the particular agent andthe delivery system used. It is understood that a toothpaste for examplewill typically be diluted with water upon use, while a mouthrinsetypically will not be. Thus, an effective concentration of active in atoothpaste will ordinarily be 5-15× higher than required for amouthrinse. The concentration will also depend on the exact salt orpolymer selected. For example, where the active agent is provided insalt form, the counterion will affect the weight of the salt, so that ifthe counterion is heavier, more salt by weight will be required toprovide the same concentration of active ion in the final product.Arginine, where present, may be present at levels from, e.g., 0.1 to 20wt % (expressed as weight of free base), e.g., 1 to 10 wt % for aconsumer toothpaste or 7 to 20 wt % for a professional or prescriptiontreatment product. Fluoride where present may be present at levels of,e.g., 25 to 25,000 ppm, for example 750 to 2,000 ppm for a consumertoothpaste, or 2,000 to 25,000 ppm for a professional or prescriptiontreatment product. Levels of antibacterial agents will vary similarly,with levels used in toothpaste being e.g., 5 to 15 times greater thanused in mouthrinse. For example, a triclosan toothpaste may contain 0.3wt % triclosan.

The oral care compositions may further include one or more fluoride ionsources, e.g., soluble fluoride salts. A wide variety of fluorideion-yielding materials can be employed as sources of soluble fluoride inthe present compositions. Examples of suitable fluoride ion-yieldingmaterials are found in U.S. Pat. No. 3,535,421, to Briner et al.; U.S.Pat. No. 4,885,155, to Parran, Jr. et al. and U.S. Pat. No. 3,678,154,to Widder et al. Representative fluoride ion sources include, but arenot limited to, stannous fluoride, sodium fluoride, potassium fluoride,sodium monofluorophosphate, sodium fluorosilicate, ammoniumfluorosilicate, amine fluoride, ammonium fluoride, and combinationsthereof. In certain embodiments the fluoride ion source includesstannous fluoride, sodium fluoride, sodium monofluorophosphate as wellas mixtures thereof. In certain embodiments, the oral care compositionmay also contain a source of fluoride ions or fluorine-providingingredient in amounts sufficient to supply 25 ppm to 25,000 ppm offluoride ions, generally at least 500 ppm, e.g., 500 to 2000 ppm, e.g.,1000 to 1600 ppm, e.g., 1450 ppm. The appropriate level of fluoride willdepend on the particular application. A toothpaste for general consumeruse would typically have 1000 to 1500 ppm, with pediatric toothpastehaving somewhat less. A dentifrice or coating for professionalapplication could have as much as 5,000 or even 25,000 ppm fluoride.Fluoride ion sources may be added to the compositions at a level of 0.01wt. % to 10 wt. % in one embodiment or 0.03 wt. % to 5 wt. %, and inanother embodiment 0.1 wt. % to 1 wt. % by weight of the composition inanother embodiment. Weights of fluoride salts to provide the appropriatelevel of fluoride ion will obviously vary based on the weight of thecounterion in the salt.

Abrasives: The oral care compositions, e.g. Composition 4 et seq. mayinclude silica abrasives, and may comprise additional abrasives, e.g., acalcium phosphate abrasive, e.g., tricalcium phosphate (Ca₃(PO₄)₂),hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂), or dicalcium phosphate dihydrate(CaBPO₄.2H₂O, also sometimes referred to herein as DiCal) or calciumpyrophosphate; calcium carbonate abrasive; or abrasives such as sodiummetaphosphate, potassium metaphosphate, aluminum silicate, calcinedalumina, bentonite or other siliceous materials, or combinationsthereof.

Other silica abrasive polishing materials useful herein, as well as theother abrasives, generally have an average particle size ranging between0.1 and 30 microns, between 5 and 15microns. The silica abrasives can befrom precipitated silica or silica gels, such as the silica xerogelsdescribed in U.S. Pat. No. 3,538,230, to Pader et al. and U.S. Pat. No.3,862,307, to Digiulio. Particular silica xerogels are marketed underthe trade name Syloid® by the W. R. Grace & Co., Davison ChemicalDivision. The precipitated silica materials include those marketed bythe J. M. Huber Corp. under the trade name Zeodent(r), including thesilica carrying the designation Zeodent 115 and 119. These silicaabrasives are described in U.S. Pat. No. 4,340,583, to Wason. In certainembodiments, abrasive materials useful in the practice of the oral carecompositions include silica gels and precipitated amorphous silicahaving an oil absorption value of less than 100 cc/100 g silica and inthe range of 45 cc/100 g to 70 cc/100 g silica. Oil absorption valuesare measured using the ASTA Rub-Out Method D281. In certain embodiments,the silicas are colloidal particles having an average particle size of 3microns to 12 microns, and 5 to 10 microns. Low oil absorption silicaabrasives particularly useful in the compositions are marketed under thetrade designation Sylodent XWA® by Davison Chemical Division of W.R.,Grace & Co., Baltimore, Md. 21203. Sylodent 650 XWA®, a silica hydrogelcomposed of particles of colloidal silica having a water content of 29%by weight averaging 7 to 10 microns in diameter, and an oil absorptionof less than 70 cc/100 g of silica is an example of a low oil absorptionsilica abrasive useful in the composition.

Foaming agents: The oral care compositions also may include an agent toincrease the amount of foam that is produced when the oral cavity isbrushed. Illustrative examples of agents that increase the amount offoam include, but are not limited to polyoxyethylene and certainpolymers including, but not limited to, alginate polymers. Thepolyoxyethylene may increase the amount of foam and the thickness of thefoam generated by the oral care carrier component of the composition.Polyoxyethylene is also commonly known as polyethylene glycol (“PEG”) orpolyethylene oxide. The polyoxyethylenes suitable for this compositionwill have a weight average molecular weight of 200,000 to 7,000,000. Inone embodiment the weight average molecular weight will be 600,000 to2,000,000 and in another embodiment, 800,000 to 1,000,000. Polyox® isthe trade name for the high molecular weight polyoxyethylene produced byUnion Carbide. The polyoxyethylene may be present in an amount of 1% to90%, in one embodiment 5% to 50% and in another embodiment 10% to 20% byweight of the oral care carrier component of the oral care compositions.Where present, the amount of foaming agent in the oral care composition(i.e., a single dose) is 0.01 to 0.9% by weight, 0.05 to 0.5% by weight,and in another embodiment 0.1 to 0.2% by weight.

Surfactants: The compositions may contain anionic, cationic, nonionicand/or zwitterionic surfactants, for example:

-   i. water-soluble salts of higher fatty acid monoglyceride    monosulfates, such as the sodium salt of the monosulfated    monoglyceride of hydrogenated coconut oil fatty acids such as sodium    N-methyl N-cocoyl taurate, sodium cocomonoglyceride sulfate,-   ii. higher alkyl sulfates, such as sodium lauryl sulfate,-   iii. higher alkyl-ether sulfates, e.g., of formula    CH₃(CH₂)_(m)CH₂(OCH₂CH₂)_(n)OSO₃X, wherein m is 6-16, e.g., 10, n is    1-6, e.g., 2, 3 or 4, and X is Na or K, for example sodium laureth-2    sulfate (CH₃(CH₂)₁₀CH₂(OCH₂CH₂)₂OSO₃Na).-   iv. higher alkyl aryl sulfonates such as sodium dodecyl benzene    sulfonate (sodium lauryl benzene sulfonate)-   v. higher alkyl sulfoacetates, such as sodium lauryl sulfoacetate    (dodecyl sodium sulfoacetate), higher fatty acid esters of 1,2    dihydroxy propane sulfonate, sulfocolaurate (N-2-ethyl laurate    potassium sulfoacetamide) and sodium lauryl sarcosinate.

By “higher alkyl” is meant, e.g., C₆₋₃₀ alkyl. In particularembodiments, the anionic surfactant is selected from sodium laurylsulfate and sodium ether lauryl sulfate. The anionic surfactant may bepresent in an amount which is effective, e.g., >0.01% by weight of theformulation, but not at a concentration which would be irritating to theoral tissue, e.g., <10%, and optimal concentrations depend on theparticular formulation and the particular surfactant. For example,concentrations used or a mouthwash are typically on the order of onetenth that used for a toothpaste. In one embodiment, the anionicsurfactant is present in a toothpaste at 0.3% to 4.5% by weight, e.g.,1.5%. The compositions may optionally contain mixtures of surfactants,e.g., comprising anionic surfactants and other surfactants that may beanionic, cationic, zwitterionic or nonionic. Generally, surfactants arethose which are reasonably stable throughout a wide pH range.Surfactants are described more fully, for example, in U.S. Pat. No.3,959,458, to Agricola et al.; U.S. Pat. No. 3,937,807, to Haefele; andU.S. Pat. No. 4,051,234, to Gieske et al. In certain embodiments, theanionic surfactants useful herein include the water-soluble salts ofalkyl sulfates having 10 to 18 carbon atoms in the alkyl radical and thewater-soluble salts of sulfonated monoglycerides of fatty acids having10 to 18 carbon atoms. Sodium lauryl sulfate, sodium lauroyl sarcosinateand sodium coconut monoglyceride sulfonates are examples of anionicsurfactants of this type. In a particular embodiment, the composition,e.g., Composition 4, et seq., comprises sodium lauryl sulfate.

The surfactant or mixtures of compatible surfactants can be present inthe composition in 0.1% to 5%, in another embodiment 0.3% to 3% and inanother embodiment 0.5% to 2% by weight of the total composition.

Note that care must be taken that the anionic surfactants do notinterfere with zinc amino acid halide complex or with the activity ofthe zinc. At relatively low levels and in a relatively low waterformulation, the surfactants generally would not have major impact, buthigher levels of anionic surfactant, particularly in aqueousformulations, anionic surfactants can be excluded. Cationic and/ornonionic surfactants may be utilized instead.

In general, the optional ingredients described herein can be present inthe first component, the second component or both.

Tartar control agents: In various embodiments, the compositions comprisean anticalcuius (tartar control) agent. Suitable anticalculus agentsinclude without limitation phosphates and polyphosphates (for examplepyrophosphates), polyaminopropanesulfonic acid (AMPS), hexametaphosphatesalts, zinc citrate trihydrate, polypeptides, polyolefin sulfonates,polyolefin phosphates, diphosphonates. The composition thus may comprisephosphate salts. In particular embodiments, these salts are alkaliphosphate salts, i.e., salts of alkali metal hydroxides or alkalineearth hydroxides, for example, sodium, potassium or calcium salts.“Phosphate” as used herein encompasses orally acceptable mono- andpolyphosphates, for example, P₁₋₆ phosphates, for example monomericphosphates such as monobasic, dibasic or tribasic phosphate; dimericphosphates such as pyrophosphates; and multimeric phosphates, e.g.,sodium hexametaphosphate. In particular examples, the selected phosphateis selected from alkali dibasic phosphate and alkali pyrophosphatesalts, e.g., selected from sodium phosphate dibasic, potassium phosphatedibasic, dicalcium phosphate dihydrate, calcium pyrophosphate,tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodiumtripolyphosphate, and mixtures of any of two or more of these. In aparticular embodiment, for example the compositions comprise a mixtureof tetrasodium pyrophosphate (Na₄P₂O₇), calcium pyrophosphate (Ca₂P₂O₇),and sodium phosphate dibasic (Na₂HPO₄), e.g., in amounts of ca. 3-4% ofthe sodium phosphate dibasic and ca. 0.2-1% of each of thepyrophosphates. In another embodiment, the compositions comprise amixture of tetrasodium pyrophosphate (TSPP) and sodium tripolyphosphate(STPP)(Na₅P₃O₁₀), e.g., in proportions of TSPP at 1-2% and STPP at 7% to10%. Such phosphates are provided in an amount effective to reduceerosion of the enamel, to aid in cleaning the teeth, and/or to reducetartar buildup on the teeth, for example in an amount of 2-20%, e.g.,ca. 5-15%, by weight of the composition,

Flavoring Agents: The oral care compositions may also include aflavoring agent. Flavoring agents which can be used in the compositioninclude, but are not limited to, essential oils as well as variousflavoring aldehydes, esters, alcohols, and similar materials. Examplesof the essential oils include oils of spearmint, peppermint,wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon,lemon, lime, grapefruit, and orange. Also useful are such chemicals asmenthol, carvone, and anethole. Certain embodiments employ the oils ofpeppermint and spearmint. The flavoring agent may be incorporated in theoral composition at a concentration of 0.1 to 5% by weight e.g. 0.5 to1.5% by weight.

Polymers: The oral care compositions may also include additionalpolymers to adjust the viscosity of the formulation or enhance thesolubility of other ingredients. Such additional polymers includepolyethylene glycols, polysaccharides (e.g., cellulose derivatives, forexample carboxymethyl cellulose, or polysaccharide gums, for examplexanthan gum or carrageenan gum). Acidic polymers, for examplepolyacrylate gels, may be provided in the form of their free acids orpartially or fully neutralized water soluble alkali metal (e.g.,potassium and sodium) or ammonium salts.

Silica thickeners, which form polymeric structures or gels in aqueousmedia, may be present. Note that these silica thickeners are physicallyand functionally distinct from the particulate silica abrasives alsopresent in the compositions, as the silica thickeners are very finelydivided and provide little or no abrasive action. Other thickeningagents are carboxyvinyl polymers, carrageenan, hydroxyethyl celluloseand water soluble salts of cellulose ethers such as sodium carboxymethylcellulose and sodium carboxymethyl hydroxyethyl cellulose. Natural gumssuch as karaya, gum arable, and gum tragacanth can also be incorporated.Colloidal magnesium aluminum silicate can also be used as component ofthe thickening composition to further improve the composition's texture.In certain embodiments, thickening agents in an amount of 0.5% to 5.0%by weight of the total composition are used.

The compositions may include an anionic polymer, for example in anamount of from 0.05 to 5%. Such agents are known generally for use indentifrice, although not for this particular application, useful incomposition are disclosed in U.S. Pat. Nos. 5,188,821 and 5,192,531; andinclude synthetic anionic polymeric polycarboxylates, such as 1:4 to 4:1copolymers of maleic anhydride or acid with another polymerizableethylenically unsaturated monomer, preferably methyl vinyl ether/maleicanhydride having a molecular weight (M.W.) of 30,000 to 1,000,000, mostpreferably 300,000 to 800,000. These copolymers are available forexample as Gantrez. e.g., AN 139 (M.W. 500,000), AN 119 (M.W. 250,000)and preferably S-97 Pharmaceutical Grade (M.W. 700,000) available fromISP Technologies, Inc., Bound Brook, N.J. 08805. The enhancing agentswhen present are present in amounts ranging from 0.05 to 3% by weight.Other operative polymers include those such as the 1:1 copolymers ofmaleic anhydride with ethyl acrylate, hydroxyethyl methacrylate,N-vinyl-2-pyrollidone, or ethylene, the latter being available forexample as Monsanto EMA No. 1103, M.W. 10,000 and EMA Grade 61, and 1:1copolymers of acrylic acid with methyl or hydroxyethyl methacrylate,methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone.Suitable generally, are polymerized olefinically or ethylenicallyunsaturated carboxylic acids containing an activated carbon-to-carbonolefinic double bond and at least one carboxyl group, that is, an acidcontaining an olefinic double bond which readily functions inpolymerization because of its presence in the monomer molecule either inthe alpha-beta position with respect to a carboxyl group or as part of aterminal methylene grouping. Illustrative of such acids are acrylic,methacrylic, ethacrylic, alpha-chloroacrylic, crotonic, beta-acryloxypropionic, sorbic, alpha-chlorsorbic, cinnamic, beta-styrylacrylic,muconic, itaconic, citraconic, mesaconic, glutaconic, aconitic,alpha-phenylacrylic, 2-benzyl acrylic, 2-cyclohexylacrylic, angelic,umbellic, fumaric, maleic acids and anhydrides. Other different olefinicmonomers copolymerizable with such carboxylic monomers includevinylacetate, vinyl chloride, dimethyl maleate and the like. Copolymerscontain sufficient carboxylic salt groups for water-solubility. Afurther class of polymeric agents includes a composition containinghomopolymers of substituted acrylamides and/or homopolymers ofunsaturated sulfonic acids and salts thereof, in particular wherepolymers are based on unsaturated sulfonic acids selected fromacrylamidoalykane sulfonic acids such as 2-acrylamide 2 methylpropanesulfonic acid having a molecular weight of 1,000 to 2,000,000, describedin U.S. Pat. No. 4,842,847, Jun. 27, 1989 to Zahid. Another useful classof polymeric agents includes polyamino acids containing proportions ofanionic surface-active amino acids such as aspartic acid, glutamic acidand phosphoserine, e.g. as disclosed in U.S. Pat. No. 4,866,161 Sikes etal.

Water: The oral compositions may comprise significant levels of water.Water employed in the preparation of commercial oral compositions shouldbe deionized and free of organic impurities. The amount of water in thecompositions includes the free water which is added plus that amountwhich is introduced with other materials.

Humectants: Within certain embodiments of the oral compositions, it isalso desirable to incorporate a humectant to prevent the compositionfrom hardening upon exposure to air. Certain humectants can also impartdesirable sweetness or flavor to dentifrice compositions. Suitablehumectants include edible polyhydric alcohols such as glycerine,sorbitol, xylitel, propylene glycol as well as other polyols andmixtures of these humectants. In one embodiment, the principal humectantis glycerin, which may be present at levels of greater than 25%, e.g.25-35% 30%), with 5% or less of other humectants.

Other optional ingredients: In addition to the above-describedcomponents, the oral care embodiments can contain a variety of optionaldentifrice ingredients some of which are described below. Optionalingredients include, for example, but are not limited to, adhesives,sudsing agents, flavoring agents, sweetening agents, additionalantiplaque agents, abrasives, and coloring agents. These and otheroptional components are further described in U.S. Pat. No. 5,004,597, toMajeti; U.S. Pat. No. 3,959,458 to Agricola et al. and U.S. Pat. No.3,937,807, to Haefele, all being incorporated herein by reference.

Other Forms

The form of the dual component system can take the form of a dualchamber form or any other means to separate the components whichinclude, but is not limited to beads, capsules, and films.

Unless stated otherwise, all percentages of composition components givenin this specification are by weight based on a total composition orformulation weight of 100%. The term “total composition” or just“composition” means the total final product form, i.e., the combinationof the first and second components.

The compositions and formulations as provided herein are described andclaimed with reference to their ingredients, as is usual in the art. Aswould be evident to one skilled in the art, the ingredients may in someinstances react with one another, so that the true composition of thefinal formulation may not correspond exactly to the ingredients listed.Thus, it should be understood that the composition extends to theproduct of the combination of the listed ingredients.

As used throughout, ranges are used as shorthand for describing each andevery value that is within the range. Any value within the range can beselected as the terminus of the range. In addition, all references citedherein are hereby incorporated by referenced in their entireties. In theevent of a conflict in a definition in the present disclosure and thatof a cited reference, the present disclosure controls.

Unless otherwise specified, all percentages and amounts expressed hereinand elsewhere in the specification should be understood to refer topercentages by weight. The amounts given are based on the active weightof the material.

Embodiments of the present invention are further described in thefollowing examples. The examples are merely illustrative and do not inany way limit the scope of the invention as described and claimed.

EXAMPLES Example A ZLC Stock Solution

18.2650 g (0.1 mole) of L-LysineHCl is dissolved in 100 ml of Deionizedwater at room temperature under stirring. After all L-LysineHCldissolves, 4.1097 g (0.0505 mole) of ZnO is slowly added into thesolution under stirring. The suspension is continued mixing at roomtemperature for at least 30 minutes to 24 hours. Then, the suspensionsolution is centrifuged at 7000 rpm for 20 minutes and filtered throughfilter membrane with 0.45 um pore size to remove unreacted ZnO. Theclear supernatant is recovered as stock solution.

Example 1

A solution 1 was prepared by dissolving 0.05 g of cysteine in 1 mL of 1M HQ solution and 10.7 g of water. A solution 2 was prepared by mixing4.95 g of ZLC stock solution with 14.85 g of glycerol.

When the two solutions were mixed, precipitation occurred with a 8seconds delay. The mixture had a final pH of 6.03.

The 8 seconds delay, as well as the delays discussed with the followingexamples, is very beneficial, because it allows ample time for thetransfer of the mixture from the mixing cup to the mouth of the userbefore the onset of the precipitation, and the precipitation occurswithin the time period a typical user would brush or rinse.

Example 2

A solution 1 was prepared by dissolving 0.05 g of cysteine in 1 mL of 1MHCl solution and 10.7 g of water. A solution 2 was prepared by mixing4.95 g of ZLC stock solution with 24.75 g of glycerol.

When the two solutions were mixed, precipitation occurred with a 8seconds delay. The mixture had a final pH of 6.17.

Example 3

A solution 1 was prepared by dissolving 0.05 g of cysteine in 1 mL of 1MHCl solution and 21.4 g of water. A solution 2 was prepared by mixing4.95 g of ZLC stock solution with 14.85 g of glycerol.

When the two solutions were mixed, precipitation occurred with a 3seconds delay. The mixture had a final pH of 6.31.

Example 4

A solution 1 was prepared by dissolving 0.05 g of cysteine in 1 mL of 1MHCl solution without added water. A solution 2 was prepared by mixing4.95 g of ZLC stock solution with 14.85 g of glycerol.

When the two solutions were mixed, precipitation occurred within 10seconds delay. The mixture had a final pH of 5.88.

Example 5

A solution 1 was prepared by mixing 0.05 g of cysteine in 1 mL of 0.0001M HCl solution, resulting in complete dissolution. The pH value of thesolution 1 was about 5.13. A solution 2 was prepared by mixing 4.95 g ofZLC stock solution and 14.85 g of glycerol.

When the two solutions were mixed, precipitation occurred in about 7seconds.

The system using 0.0001 M HCl solution is preferred over theabove-mentioned systems involving 1M HCl, because the solution 1prepared from 1 mL of 1M HCl is substantially lower in pH value fromthat prepared using 1 mL of 0.0001M HCl solution. For example, asolution of 0.05g of cysteine in 1 mL of 1M HCl has a pH of about 1.15.If the acid strength is reduced to 0.1 M, the pH is 2.44. If the acid isat 0.01M, the pH is 3.62. If the acid is supplied at 0.001 M, the pH is4.89. Although preparations using these acid levels will work indelaying the precipitation times, they are less safe as compared to thepreparation using 0.0001M HCl, with a pH of 5.13.

Example 6

A solution 1 was prepared by mixing 0.05 g of cysteine, 1 mL of 0.0001 MHCl solution, and glycerol so that the total mass of the solution 1 was19.8 g. A solution 2 was prepared by mixing 4.95 g of ZLC stock solutionand 14.85 g of glycerol.

When the two solutions were mixed, precipitation took place after asignificant delay. Cloudiness occurred about 12 second after mixing, andthe mixture stopped turning more cloudy about 20 seconds after mixing.

a. Surface Deposition and Occlusion of Dentine Tubules Using SystemsContaining ZLC, Cysteine, HCL and Glycerol

The dual-component system proved effective in occluding dentine tubulesin in-vitro assays.

A first solution was prepared by mixing 0.05 g of cysteine with 1 mL of0.0001 M HCl solution. A second solution was prepared by mixing 4.95 gof ZLC stock solution with 14.85 g of glycerol. The two stock solutionswere mixed in the presence of dentine slices. The dentine slices wereprepared by cutting human tooth into thin dentine sections of about 800microns in thickness, choosing a test side, sanding said test side usinga sandpaper of about 600 grit, polishing said test side using a Buehlerpolishing cloth and 5 micron Buehler aluminum oxide, acid-etching saiddentine section in 1% (by weight) citric acid solution for about 20seconds, sonicating said dentine section for 10 minutes, and storingsaid dentine section in phosphate buffered saline (PBS, pH 7.4).

The dentine slices were examined under confocal microscope in XYZ andXZY mode for surface deposition and occlusions of tubules at theiropenings.

It was discovered that during six consecutive treatments andexaminations, there was progressively more deposition of particles onthe dentine surface, and progressively more accumulation of particleswithin tubules and around the tubule openings.

The surface deposition leads to benefits such as erosion protection, aswell as providing a reservoir of zinc ions for controlled release.

The occlusion of tubules leads to benefits such as sensitivity relief,as well as providing the same reservoir.

The dentine section is dried and examined under a Spectroshade™spectrophotometer (Handy Dental Type 71,3000). The treated dentinal areais included and the enamel rim is excluded from the examination andsubsequent data processing. The CIELAB color reading is obtained. It iscommonly understood that, by definition, L*=0 means black and L*=T00indicates diffuse white, negative a* value indicates green whilepositive values indicate magenta, and negative b* values indicate blueand positive values indicate yellow. It is noted that the successivesurface deposition led to a slight increase in L* values of the surface(from 69.1 at baseline to about 7.1.8 after 6 treatments), an indicationof slight increase in whiteness.

b. Ineffectiveness of Methionine in Changing Precipitation Time of ZLCChelates

Among the sulfur-containing amino acids, cysteine is the only one thatis capable of adjusting precipitation time of ZLC Methionine has noeffect.

In a first example, a solution 1 was prepared from 0.05 g methionine and1 ml, of 0.0001M HCl solution. A solution 2 was prepared from 4.95 g ofZLC stock solution and 14.85 g of glycerol. When the two solutions weremixed, no precipitation occurred. The same system using cysteine insteadof methionine resulted in precipitation.

In a second example, a solution 1 was prepared from 0.05 g ofmethionine, and 1 mL of 1M HCl solution. A solution 2 was prepared from4.95 g of ZLC stock, solution and 14.85 g of glycerol. When the twosolutions were mixed, no precipitation occurred.

In a third example, a solution 1 was prepared from 0.05 g of methionine,and 1 mL of 0.0001M HCl solution. A solution 2 was prepared from 4.95 gof ZLC stock solution with no glycerol, so that the rate of the reactioncan be enhanced. No precipitation occurred upon mixing.

It is contemplated that any other compounds with an available terminal—SH functional group may be used in place or in combination withcysteine for the present invention. Such compounds include amino aciddimers, trimers, oligomers, or polymers, i.e., peptides and proteinsthat contain at least one terminal —SH functional group.

Example 7 Liquid Hand Soap with ZLC

1 g of ZLC-Cys solution of Example 4 (prior to dilution to form the“stock” solution) is combined with 4 g of a commercial liquid hand soap(LHS) having a formulation as set forth in Table 6, to provide aformulation having 0.7% zinc.

TABLE 1 Material Weight % Cetrimonium chloride (cetyl trimethyl ammoniumchloride) 2.4 Glycerin 2 Lauramidopropyldimethylamine oxide 1.2 CocamideMEA (cocomonoethanolamide) 1 PEG-120 methyl glucose dioleate 0.6Myristamidopropylamine oxide 0.4 C₁₂₋₁₈ alkydimethylbenzyl ammoniumchloride (BKC) 0.13 Water and optional ingredients Q.S.In a soap container, the bottle is divided by a of barrier. Both sidesof the barrier contain the standard soap base in the table immediatelyabove. One side contains the appropriate amount of cysteine and theother side contains the appropriate amount of ZLC. When dispensed, thetwo stocks will mix in the nozzle forming an instantaneous precipitationdirectly to the skin's surface without having a reaction occur withinthe bottle that may expend all the desired benefits.

Example 8 Gel Formulations Comprising Zinc-Lysine

An oral gel toothpaste with ZLC/cysteine as active ingredient isformulated. The precipitation property of ZLC gel phase is alsoinvestigated by hydrolysis reaction study, to determine whether when theteeth are being brushed with toothpaste containing ZLC/cysteine, theinsoluble particles formed during brushing can penetrate into the dentintubules and block the tubules resulting in an anti-sensitivity effectand signal for the consumer.

A gel with ZLC/cysteine as active ingredient is formulated with theingredients shown in Table 2. The clarity and the precipitation bydilution is evaluated. Zinc ion concentration in the following batchesis at 0.5% (w/w) zinc level.

TABLE 2 Oral gel with ZLC/cysteine Ingredients % Loading (g) Sorbitol70% sol 76.03%  380.15 Aqueous ZLC solution 2.53% Zn plus 0.5% 20.00% 100 cysteine Carboxymethyl cellulose (CMC) and 0.70% 3.5 Trimethylcellulose (TMC) Na Saccharin 0.27% 1.35 Propylene Glycol 3.00% 15 Total100.00%  500 % Zn 0.506% The ingredients are placed in a tube. The tube is separated by means ofeither a physical divider resulting in two chambers, one chambercontaining cysteine and the other containing ZLC. When dispensed, theformulation does not react due to the appropriate desired delay. Uponmixing and brushing a precipitate forms to occlude tubules and provideszinc ion benefits to the oral surfaces.

1. A dual component composition to deliver zinc to a body whichcomprises (i) a first component comprising a zinc-ammo acid-halidecomplex or a zinc-trialkyl glycine-halide complex, and (ii) a secondcomponent comprising cysteine in free or in orally or cosmeticallyacceptable salt form, the first and second components being maintainedseparate from each other until dispensed and combined for application tothe body.
 2. The dual component composition of claim 1 furthercomprising glycerol in the first component, in the second component orin both components.
 3. The dual component composition according to claim1 wherein the pH of the first component is 7 to 9 and the pH of thesecond component is 3 to
 6. 4. The composition according to claim 1wherein the zinc-amino acid-halide complex or a zinc-trialkyl)glycine-halide complex is formed from precursors, wherein the precursorsare a zinc ion source, an amino acid or trialkyl glycine source, and ahalide source, wherein the halide source can be part of the zinc ionsource, the amino acid or trialkyl glycine source, or a halogen acid. 5.The composition according to claim 4, wherein the zinc ion source is atleast one of zinc oxide, zinc chloride, zinc carbonate, zinc nitrate,zinc citrate, and zinc phosphate.
 6. The composition according to claim4, wherein the amino acid source is at least one of a basic amino acid,lysine, arginine, and glycine.
 7. The composition, according to claim 1,wherein the trialkyl glycine is a C₁-C₄ alkyl glycine or trimethylglycine.
 8. The composition according to claim 1 wherein the zinc-aminoacid-halide complex is made by combining zinc oxide with an amino acidhydrohalide.
 9. The composition according to claim 1 wherein the zinc(amino acid or trialkyl glycine) halide complex has the formula Zn(aminoacid or trialkyl glycine)₂Hal₂ or Zn(amino acid or trialkyl glycine)₃Hal₂, wherein Zn is a divalent zinc ion and Hal is a halide ion.
 10. Thecomposition according to claim 1 wherein the zinc-amino acid-halidecomplex is [Zn(C₆H₁₄N₂O₂)₂Cl]⁺Cl⁻.
 11. The composition according toclaim 1 wherein the amount of cysteine is 0.1% to 1%.
 12. Thecomposition according to claim 1, wherein the cysteine is cysteinehydrohalide, optionally cysteine hydrochloride.
 13. The compositionaccording to claim 1 which upon mixing the two components, provides aprecipitate comprising zinc oxide in complex with cysteine, andoptionally additionally comprising zinc oxide, zinc carbonate, andmixtures thereof.
 14. The composition according to claim 1, which uponmixing the two components, forms a precipitate in about 1 to about 20seconds after mixing.
 15. The composition according to claim 1 whereinthe total amount of zinc present in the composition is selected from theranges of 0.2 to 8% by weight, 0.1 to 8 weight %, 0.1 to 2 and 0.1 to 1weight % of the total composition.
 16. The composition according toclaim 1 wherein the dual component is selected from the group consistingof dual chamber, beads, capsules, and films.
 17. The compositionaccording to claim 1 which is an antiperspirant or deodorant product,further comprising a cosmetically acceptable carrier.
 18. A method ofkilling bacteria, reducing perspiration, and/or reducing body odorcomprising mixing the two components of claim 17 and applying to skin aneffective amount of the mixed components.
 19. The composition of claim1, which is a personal care product selected from liquid hand soap, bodywash, dermal lotions, dermal creams, and dermal conditioners furthercomprising a cosmetically acceptable carrier in the first component, thesecond component, or in both components.
 20. A method of killingbacteria, treating or reducing the incidence of acne or topical skininfections, or to provide a visual signal when washing, comprisingmixing the two components of claim 19 and then washing the skin withwater and an effective amount of the mixed components.
 21. Thecomposition of claim 1 which is an oral care product, further comprisingan orally acceptable carrier in the first component, the secondcomponent, or in both components.
 22. A method to reduce and inhibitacid erosion of the enamel, clean the teeth, reducebacterially-generated, biofilm and plaque, reduce gingivitis, inhibittooth decay and formation of cavities, and/or reduce dentinalhypersensitivity comprising mixing the components of claim 21 andapplying an effective amount of the mixed components to the oral cavityof a person in need thereof.
 23. A method of manufacturing anantiperspirant or deodorant product, a personal care product or an oralcare product which comprises a dual component composition according toclaim 1, comprising the step of incorporating a zinc-amino acid-halidecomplex or a zinc-trialkyl glycine-halide complex in one component, andcysteine in free or orally acceptable salt form in a second component,during manufacture of the composition.